Document Detail


Flow-dependent channel formation in clots by an erythrocyte-bound fibrinolytic agent.
MedLine Citation:
PMID:  21389322     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Studies in animal models have shown that plasminogen activators bound to erythrocytes (RBC-PA) have an extended lifetime in the circulation and are safer than free PAs. RBC-PAs incorporate into nascent thrombi, which are focally lysed from within, an attractive thromboprophylactic option. In static systems, RBC-PAs cleave surrounding fibrin fibers, forming pores larger than the cells themselves, and move around the pore edges, enlarging them until eventual clot dissolution. We hypothesized that under flow in blood vessels, RBC-PAs form functional patent channels before clot dissolution. Here we used perfusion chambers to study clot lysis by RBC-PAs under static versus arterial and venous flow conditions. We found that flow decelerates bulk clot lysis but quickly generates patent channels filled with passing RBCs, via pore enlargement and merging in the direction of flow. Formation of such channels by RBC-PAs may help rescue ischemic tissue before bulk dissolution of potentially occlusive clots.
Authors:
Kathryn C Gersh; Sergei Zaitsev; Douglas B Cines; Vladimir Muzykantov; John W Weisel
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural     Date:  2011-03-09
Journal Detail:
Title:  Blood     Volume:  117     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-05-06     Completed Date:  2011-07-05     Revised Date:  2012-05-08    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4964-7     Citation Subset:  AIM; IM    
Affiliation:
Department of Cell & Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Blood Coagulation / drug effects*,  physiology
Erythrocytes / drug effects,  physiology
Fibrinolytic Agents / pharmacology*
Hemorheology
Humans
Mice
Microscopy, Confocal
Models, Biological
Plasminogen Activators / pharmacology
Grant Support
ID/Acronym/Agency:
HD-057355/HD/NICHD NIH HHS; HL-076406/HL/NHLBI NIH HHS; HL-077760/HL/NHLBI NIH HHS; HL090774/HL/NHLBI NIH HHS; HL30954/HL/NHLBI NIH HHS; R01 HL090774-04/HL/NHLBI NIH HHS; R01-HL090697/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Fibrinolytic Agents; EC 3.4.21.-/Plasminogen Activators

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Low but sustained coagulation activation ameliorates glucose induced podocyte apoptosis: protective ...
Next Document:  Aptamer ARC19499 mediates a procoagulant hemostatic effect by inhibiting tissue factor pathway inhib...